Distinct clinical characteristics in stage III rectal cancer among different age groups and treatment outcomes after neoadjuvant chemoradiotherapy

Abstract

Background: There is a rapidly increasing incidence of early-onset colorectal cancer (EO-CRC) which threatens the survival of young people, while aging also represents a challenging clinical problem.

Objectives: We aimed to investigate the differences in the clinical characteristics and prognosis in stage III rectal cancer (RC), to help optimize treatment strategies.

Design and methods: This study included 757 patients with stage III RC, all of whom received neoadjuvant chemoradiotherapy and total mesorectal excision. The whole cohort was categorized as very early onset (VEO, ⩽30 years old), early onset (EO, >30 years old, ⩽50 years old), intermediate onset (IO, >50 years, ⩽70 years), or late onset (LO, >70 years old).

Results: There were more female VEO patients than males, more mucinous adenocarcinoma, signet-ring cell carcinoma, pre-treatment cT4 stage, and higher pre-treatment serum carbohydrate antigen 19-9 compared with the other three groups. VEO patients had the worst survival with the highest RC-related mortality (34.5%), recurrence (13.8%), and metastasis (51.7%). LO patients had the highest non-RC-related mortality rate (16.6%). The Cox regression model showed VEO was a negative independent prognostic factor for disease-free survival [DFS, hazard ratio (HR): 2.830, 95% confidence interval (CI): 1.633-4.904, p < 0.001], distant metastasis-free survival (DMFS, HR: 2.969, 95% CI: 1.720-5.127, p < 0.001), overall survival (OS, HR: 2.164, 95% CI: 1.102-4.249, p = 0.025), and cancer-specific survival (CSS, HR: 2.321, 95% CI: 1.145-4.705, p = 0.020). LO was a negative independent factor on DFS (HR: 1.800, 95% CI: 1.113-2.911, p = 0.017), DMFS (HR: 1.903, 95% CI: 1.150-3.149, p = 0.012), OS (HR: 2.856, 95% CI: 1.745-4.583, p < 0.001), and CSS (HR: 2.248, 95% CI: 1.282-3.942, p = 0.005). VEO patients had better survival in the total neoadjuvant therapy-like (TNT-like) pattern on DFS (p = 0.039). IO patients receiving TNT-like patterns had better survival on DFS, OS, and CSS (p = 0.006, p = 0.018, p = 0.006, respectively).

Conclusion: In stage III RC, VEO patients exhibited unique clinicopathological characteristics, with VEO a negative independent prognostic factor for DFS, DMFS, OS, and CSS. VEO and IO patients may benefit from a TNT-like treatment pattern.

Keywords: onset age; prognosis; rectal cancer; stage III; total neoadjuvant therapy.

Figure 1.

The patient screening flow diagram. ACT, adjuvant chemotherapy; NACRT, neoadjuvant chemoradiotherapy; PTV, planning target volume; TME, total mesorectal excision.

Figure 2.

Survival analysis for the four-onset age groups with stage III rectal cancer on (a) DFS, (b) DMFS, (c) LRFS, (d) OS, and (e) CSS. CSS, cancer-specific survival; DFS, disease-free survival; DMFS, distant metastasis-free survival; LRFS, local recurrence-free survival; OS, overall survival.

Figure 3.

Survival analysis of stage III rectal cancer patients receiving different treatment patterns. Comparison of the CRT-like and TNT-like patterns of very early onset on (a) DFS, (b) OS, and (c) CSS. Comparison of the CRT-like and TNT-like patterns of early onset on (d) DFS, (e) OS, and (f) CSS. Comparison of the CRT-like and TNT-like patterns for intermediate onset on (g) DFS, (h) OS, and (i) CSS. Comparison of the CRT-like and TNT-like patterns for late onset on (j) DFS, (k) OS, and (l) CSS. CRT, chemoradiotherapy; CSS, cancer-specific survival; DFS, disease-free survival; OS, overall survival; TNT, total neoadjuvant treatment.